Development of ITI-333, a μ-opioid Receptor Partial Agonist and 5HT2A and D1 Receptor Antagonist, for the Treatment of Opioid Use Disorders

开发 ITI-333,一种 μ-阿片受体部分激动剂和 5HT2A 和 D1 受体拮抗剂,用于治疗阿片类药物使用障碍

基本信息

  • 批准号:
    9841388
  • 负责人:
  • 金额:
    $ 291.71万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-01-01 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

RFA-DA-19-002 Principal Investigator/PD: Vanover, Kimberly E. Project Summary/Abstract Intra-Cellular Therapies Inc (ITI), a clinical-stage biopharmaceutical company, is developing ITI-333, a novel compound with high affinity activity at mu opiate (MOP), 5-HT2A, and D1 receptors. The nonclinical profile of ITI-333 suggests a promising medication, lacking abuse liability, with partial agonist activity at MOP receptors useful for treatment of opiate withdrawal in individuals with Opioid Use Disorders (OUD). ITI is currently completing IND-enabling nonclinical safety, toxicology, pharmacokinetic and manufacturing activities, with the goal of launching Phase 1 human clinical evaluation of ITI-333 in healthy volunteers in Q1 2019. ITI seeks to partner with NIDA in the development of this compound for a novel and safe therapeutic for use in treating OUD, requesting support of clinical development of ITI-333, while committing significant internal funds to a parallel program of non-clinical development and CMC activities in support of the clinical plan. To this end, we submit this application, “Development of ITI-333, a µ-opioid Receptor Partial Agonist and 5HT2A and D1 Receptor Antagonist, for the Treatment of Opioid Use Disorders” to NIDA RFA-DA-19-002, Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3). Here, we propose a 2-year UG3 program, including a First-in-Man, single ascending dose (SAD) study (ITI-333-001) to assess the safety, tolerability and pharmacokinetics of ITI-333 in healthy volunteers. The safety, tolerability, and pharmacokinetics of multiple, ascending doses (MAD) of ITI-333 will then be evaluated in a single-center in-patient study (ITI-333-002) with the goal of determining a maximally- tolerated dose (MTD). Both studies will be conducted in collaboration with Clinilabs, a NYC-based CRO. In parallel with the MAD study, we will characterize the in vivo receptor pharmacology of ITI-333 at MOP, 5- HT2A, and D1 receptors in human brain using PET imaging (with Dr. Dean Wong, JHU, ITI-333-003), thereby leveraging our SAD data to clinically validate the mechanism of action of ITI-333 and to inform Phase 2 dose selection. These data will enable us to launch a 3-year UH3 program exploring the human abuse liability (HAL) and functional pharmacology of ITI-333 in collaboration with Dr. Sandra Comer (CUMC), a clinical expert in opioid use and abuse. The HAL study (Phase 2a, ITI-333-004) will characterize the opioid receptor antagonist/partial agonist profile of ITI-333 in humans to explore potential abuse liability in humans. Additional Phase 2 studies will evaluate the in vivo functional pharmacology of ITI-333 in a model of withdrawal precipitation in non-treatment seeking heroin users (ITI-333-005) and in a model of mu-opioid receptor blockade in treatment-seeking heroin users (ITI-333-006). Together, we believe this clinical development plan with inform further development of ITI-333 and the selection of a cogent Phase 3 clinical path toward FDA approval as a medication for the treatment of OUD.
RFA-DA-19-002主要研究者/PD:Vanover、Kimberly E. 项目总结/摘要 细胞内治疗公司(ITI),一家临床阶段的生物制药公司,正在开发ITI-333,一种新的 对μ阿片(MOP)、5-HT 2A和D1受体具有高亲和力活性的化合物。的非临床特征 ITI-333表明是一种有前途的药物,无滥用倾向,在MOP下具有部分激动剂活性 用于治疗阿片类药物使用障碍(OUD)个体的阿片类药物戒断的受体。ITI正在 目前正在完成IND使能性非临床安全性、毒理学、药代动力学和生产 活动,目标是在第一季度在健康志愿者中启动ITI-333的1期人体临床评价 2019. ITI寻求与NIDA合作开发这种化合物,用于新型安全的治疗 用于治疗OUD,请求支持ITI-333的临床开发,同时承诺 内部资金用于非临床开发和CMC活动的平行计划,以支持临床 计划为此,我们提交了这份申请,“开发ITI-333,一种μ-阿片受体部分 激动剂和5 HT 2A和D1受体拮抗剂,用于治疗阿片类药物使用障碍”至NIDA RFA-DA-19-002,预防和治疗阿片类药物使用障碍和过量的药物开发 (UG3/UH3)。在这里,我们提出了一个为期2年的UG 3计划,包括首次在人,单次剂量递增 (SAD)评估ITI-333在健康受试者中的安全性、耐受性和药代动力学的研究(ITI-333-001) 志愿者多次递增剂量(MAD)ITI-333的安全性、耐受性和药代动力学将 然后在单中心住院患者研究(ITI-333-002)中进行评价,目的是确定最大- 耐受剂量(MTD)。这两项研究都将与纽约市的CRO Clinilabs合作进行。在 与MAD研究平行,我们将描述ITI-333在MOP,5- HT 2A和D1受体在人脑中使用PET成像(与Dean Wong博士,JHU,ITI-333-003),从而 利用我们的SAD数据在临床上验证ITI-333的作用机制,并为第2阶段提供信息 剂量选择这些数据将使我们能够启动一个为期3年的UH 3项目,探索人类虐待 责任(HAL)和ITI-333的功能药理学与Sandra Comer博士(CNODC)合作, 阿片类药物使用和滥用方面的临床专家。HAL研究(2a期,ITI-333-004)将描述阿片类药物 受体拮抗剂/部分激动剂特性,以探索人类中的潜在滥用倾向。 另外的2期研究将评估ITI-333的体内功能药理学, 非寻求治疗的海洛因使用者(ITI-333-005)和μ阿片类药物模型中的戒断沉淀 寻求治疗的海洛因使用者中的受体阻滞(ITI-333-006)。我们相信,这种临床 开发计划,包括ITI-333的进一步开发和选择令人信服的3期临床试验 通往FDA批准作为治疗OUD的药物的道路。

项目成果

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{{ truncateString('SANDRA D COMER', 18)}}的其他基金

Transcutaneous Phrenic Nerve Stimulation for Treating Opioid Overdose
经皮膈神经刺激治疗阿片类药物过量
  • 批准号:
    10681111
  • 财政年份:
    2023
  • 资助金额:
    $ 291.71万
  • 项目类别:
Phase 1 and 2 studies of sublingual dexmedetomidine, an alpha 2 adrenergic agonist, for treating opioid withdrawal
舌下含服右美托咪定(一种 α2 肾上腺素能激动剂)用于治疗阿片类药物戒断的 1 期和 2 期研究
  • 批准号:
    10478324
  • 财政年份:
    2022
  • 资助金额:
    $ 291.71万
  • 项目类别:
Development of a monoclonal antibody to reverse overdose from fentanyl and its analogs: from manufacturing to clinical trials
开发逆转芬太尼及其类似物过量的单克隆抗体:从制造到临床试验
  • 批准号:
    10615519
  • 财政年份:
    2022
  • 资助金额:
    $ 291.71万
  • 项目类别:
Phase 1a/1b Clinical Trials of Multivalent Opioid Vaccine Components
多价阿片类疫苗成分的 1a/1b 期临床试验
  • 批准号:
    10782616
  • 财政年份:
    2018
  • 资助金额:
    $ 291.71万
  • 项目类别:
CERC-501 Kappa Antagonist for Nicotine Dependence
CERC-501 尼古丁依赖性 Kappa 拮抗剂
  • 批准号:
    9041849
  • 财政年份:
    2016
  • 资助金额:
    $ 291.71万
  • 项目类别:
Dynamic Contrast-Enhanced MRI to Measure Blood-Brain Barrier Permeability in Substance Abusers
动态对比增强 MRI 测量药物滥用者的血脑屏障渗透性
  • 批准号:
    9066619
  • 财政年份:
    2015
  • 资助金额:
    $ 291.71万
  • 项目类别:
Dynamic Contrast-Enhanced MRI to Measure Blood-Brain Barrier Permeability in Substance Abusers
动态对比增强 MRI 测量药物滥用者的血脑屏障渗透性
  • 批准号:
    8989439
  • 财政年份:
    2015
  • 资助金额:
    $ 291.71万
  • 项目类别:
Risk and Benefits of Overdose Education and Naloxone Prescribing to Heroin Users
过量教育和向海洛因使用者开纳洛酮处方的风险和益处
  • 批准号:
    8694865
  • 财政年份:
    2014
  • 资助金额:
    $ 291.71万
  • 项目类别:
Risk and Benefits of Overdose Education and Naloxone Prescribing to Heroin Users
过量教育和向海洛因使用者开纳洛酮处方的风险和益处
  • 批准号:
    9330829
  • 财政年份:
    2014
  • 资助金额:
    $ 291.71万
  • 项目类别:
Laboratory Model for Heroin Abuse Medications
海洛因滥用药物的实验室模型
  • 批准号:
    7628363
  • 财政年份:
    2008
  • 资助金额:
    $ 291.71万
  • 项目类别:

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